Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Phase Ib Trial of a Maintenance Multipeptide Vaccine (S-588210) in Patients With Unresectable Malignant Pleural Mesothelioma Without Progression After First-Line Chemotherapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02661659
Recruitment Status : Withdrawn (PI stopped study due to inability to accrue.)
First Posted : January 22, 2016
Last Update Posted : May 14, 2018
Sponsor:
Information provided by (Responsible Party):
University of Chicago

Tracking Information
First Submitted Date  ICMJE January 20, 2016
First Posted Date  ICMJE January 22, 2016
Last Update Posted Date May 14, 2018
Actual Study Start Date  ICMJE June 12, 2016
Actual Primary Completion Date October 3, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 20, 2016)
Proportion of patients who show in vitro cytotoxic T lymphocyte induction to at least 2 of the 5 antigens determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay [ Time Frame: Within 8 months from initiation of vaccination ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 20, 2016)
  • Toxicity per Common Terminology Criteria for Adverse Events (CTCAE) v4.03 [ Time Frame: Up to 4 weeks ]
  • Disease control rate defined as the proportion of patients who are assessed as having complete response (CR), partial response (PR), or stable disease (SD) (>3 months) [ Time Frame: 6 months ]
  • 6-month progression-free survival (PFS) rate [ Time Frame: 6 months ]
  • Peptide-specific cytotoxic T lymphocyte response determined by Enzyme-Linked ImmunoSpot (ELISPOT) assay [ Time Frame: At 2, 3, 4, 6 and 8 months of vaccination ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase Ib Trial of a Maintenance Multipeptide Vaccine (S-588210) in Patients With Unresectable Malignant Pleural Mesothelioma Without Progression After First-Line Chemotherapy
Official Title  ICMJE A Phase Ib Trial of a Maintenance Multipeptide Vaccine (S-588210) in Patients With Unresectable Malignant Pleural Mesothelioma Without Progression After First-Line Chemotherapy
Brief Summary A phase Ib study investigating the safety, the immunogenicity and the optimal administration frequency of the S-588210 5-peptide vaccine in MPM patients without progression after pemetrexed-based chemotherapy will be conducted. Additionally, to identify more accurate predictive biomarkers of response to S-588210, T-cell-receptor-sequencing (TCR) pre- and post-vaccination will be performed in blood samples of patients treated with the vaccine. Immunohistochemical analysis of the vaccine oncoantigens will also be correlated with induction of antigen-specific T-cell responses. Finally, to explore the infiltration of tumors with T-cells and the potential presence of an immunosuppressive tumor microenvironment, immunohistochemistry for immune checkpoints (including PDL1/PD1, CTLA4) and immune suppressive cell subsets (T-regs, macrophages) will be performed.
Detailed Description

Primary Objective:

To evaluate the rate of peptide-specific CTL induction to S-588210 within the first 8 months in HLA-A*02:01-positive patients with MPM who have not progressed on first-line pemetrexed-based chemotherapy treated on a weekly or every other week vaccination schedule.

Secondary Objectives:

  1. To evaluate the safety of S-588210 in HLA-A*02:01-positive patients with MPM treated with S-588210
  2. To determine the disease control rate (DCR) in HLA-A*02:01-positive patients with MPM treated with S-588210
  3. To determine the progression-free-survival (PFS) in HLA-A*02:01-positive patients with MPM who have not progressed on first-line pemetrexed-based chemotherapy and who are treated with S-588210
  4. To evaluate the peptide-specific CTL response to S-588210 over time up to 8 months in HLA-A*02:01-positive patients with MPM who have not progressed on first-line pemetrexed-based chemotherapy
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Malignant Pleural Mesothelioma (MPM)
Intervention  ICMJE Biological: Multipeptide vaccine S-588210
Study Arms  ICMJE
  • Weekly Vaccination
    Maintenance multipeptide vaccine (S-588210) administered every week
    Intervention: Biological: Multipeptide vaccine S-588210
  • Every other Week Vaccination
    Maintenance multipeptide vaccine (S-588210) administered every other week
    Intervention: Biological: Multipeptide vaccine S-588210
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: May 10, 2017)
0
Original Estimated Enrollment  ICMJE
 (submitted: January 20, 2016)
16
Actual Study Completion Date  ICMJE October 3, 2017
Actual Primary Completion Date October 3, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with unresectable MPM that have completed 4-6 cycles of standard first-line pemetrexed-based chemotherapy for at least 1 month and have not progressed
  • Age>18
  • Able to provide informed consent for the study
  • HLA-A*02:01 positive
  • ECOG PS=0-1 at enrollment
  • Measurable indicator lesion by modified RECIST criteria
  • Adequate bone marrow (ANC > 1000cells/ml, PLT > 50,000/ml, Hg > 8gr/dL), renal (Cr > 2.5xUNL) and liver function (AST, ALT< 3x UNL, total bilirubin < 2x UNL, ALP < 3x UNL)
  • Archival tumor tissue available for IHC (1 paraffin-embedded block)
  • Epithelioid or biphasic histology

Exclusion Criteria:

  • Chemotherapy or investigational antineoplastic drug within 1 month of planned initiation of vaccine therapy
  • Patients who received DEPDC1, MPHOSPH1, URLC10, CDCA1, or KOC1 peptide vaccines before
  • Active treatment with corticosteroids or other immunosuppressive agents
  • Patients who are expected to require any of the following therapies between enrollment and completion or discontinuation of the study treatment:

    1. immunosuppressive drugs, including corticosteroids, methotrexate, mercaptopurine, azathioprine, cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, ATG (anti-thymoglobulin), IL2-receptor antibodies (basiliximab, daclizumab), TNF-a antibodies (infliximab, etanercept, adalimumab)
    2. radiotherapy for the target disease
    3. surgical therapy for the target disease
  • History of bone marrow transplantation
  • Active infection
  • Human immunodeficiency virus infection
  • History of or active systemic autoimmune disorder or immunodeficiency syndromes
  • History of severe (CTCAE v.4.03 grade 3 or higher) allergic reaction to a drug, vaccination, or biological preparation.
  • Pregnancy
  • Patients who cannot or do not intend to practice effective contraception
  • Severe illness requiring hospitalization
  • Lymphocytes <15% of total WBCs at baseline
  • Sarcomatoid histology
  • Severe (CTCAE v.4.03 grade 3 or higher) concurrent hepatic impairment, renal impairment, heart disease, hematological disease, respiratory disease, or metabolic disease
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02661659
Other Study ID Numbers  ICMJE IRB14-1519
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Chicago
Study Sponsor  ICMJE University of Chicago
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account University of Chicago
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP